: Azo dyes, as a major group of the synthetic colorants, are added to food products not only to make them aesthetic but also to preserve their appearance. However, the use of azo dyes in food has been banned worldwide due to side effects on human health. The search was conducted using PubMed, Scopus, Web of Science, Europe PMC beta, Science Direct, and Springer database considering all articles published up to 9 July 2021. The inclusion criteria were double-blind, randomized, cohort studies, placebo-controlled trials, case reports, non-controlled trials, and case series. Several studies suggest that azo dyes induce oxidative stress, which subsequently increases the concentration of malondialdehyde and reduces superoxide dismutase (SOD) activity and glutathione (GSH) concentration in brain tissue. Also, results showed the adverse effects of azo dyes on the brain parts such as the prefrontal cortex, cerebellum, and cerebrum which, are accompanied by changes in brain function. It can be concluded that azo dyes with an increase in oxidative stress affect the most important parts of the brain and cause brain dysfunction. This study aimed to evaluate the effects of the food additive azo dyes on brain tissues.